Abstract CT025: JS203, a CD20×CD3 bispecific antibody with a 2:1 structure, demonstrated promising responses in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) in a phase I study

Abstract Purpose: JS203 is a 2:1 bispecific antibody that targets both CD20 and CD3, exhibiting a lower affinity for CD3. This Phase I study (NCT05618327) aimed to evaluate the safety, tolerability, and efficacy of JS203 in R/R B-NHL. Data from both the dose-escalation and dose-expansion phases are presented. Methods: Patients with pathologically diagnosed CD20-positive B-NHL who had received at least one prior lymphoma treatment were eligible for the study. JS203 was administered with a weekly step-up dosing (SUD) during the first 28 days of Cycle 1, followed by administration every three weeks until disease progression or unacceptable toxicity. A single dose of rituximab or its biosimilar was given three days before the first dose of JS203 to mitigate cytokine release syndrome (CRS) in the two highest dose groups. Dose escalation was conducted using accelerated titration and the Bayesian Optimal Interval (BOIN) method. The primary endpoints included the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Results: As of December 23, 2024, a total of 48 patients were enrolled in the study. The majority of these patients were diagnosed with diffuse large B-cell lymphoma (60.4%) and follicular lymphoma (29.2%) and had received a median of three prior therapies. Doses up to 30 mg were evaluated in the study, and the MTD was not reached. Twenty patients did not receive rituximab as pre-treatment, and 13 (65%) of these developed CRS. In comparison, twenty-eight patients received pre-treatment with rituximab, of whom only 11 (39.3%) developed CRS. Among the patients pretreated with rituximab, the most common drug-related adverse events occurred in at least 20% of patients, including anemia (42.9%), CRS (39.3%), decreased neutrophil count (25.0%), decreased lymphocyte count (25.0%) and decreased white blood cell count (21.4%). All cases of CRS were classified as Grade 1-2 and had resolved by the data cutoff. None of the patients developed immune effector cell-related neurotoxicity syndrome. Among patients receiving doses of 0.4 mg or higher, the overall response rate (ORR) was 46.2% (12 out of 26), and it was 100% (3 out of 3) at the 30 mg dose level. Conclusion: JS203 SUD administration, when pretreated with rituximab, demonstrated a favorable safety profile and promising responses in patients with R/R B-NHL. CRS were mostly mild and primarily occurred in Cycle 1. Responses were observed even at very low dose levels and expansion at the 30 mg dose level is ongoing. Citation Format: Yan Xie, Hongming He, Hongmei Jing, Haiyan Yang, Huangming Hong, Yufu Li, Yuerong Shuang, Liqun Zou, Jian Li, Li Yu, Qi Deng, Dexiao Kong, Zengjun Li, Zhifang Liu, Xin Wang, Xiaojing Yan, Yifan Wang, Weiwei Wang, Tong Lu, Shuanghui Wei, Zhihao Jiang, Yuqin Song. JS203, a CD20×CD3 bispecific antibody with a 2:1 structure, demonstrated promising responses in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) in a phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT025.